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Journal : Narra X

In silico design of a multi-epitope rabies vaccine candidate incorporating African HLA diversity: A reverse vaccinology approach Afnani, Moh R.; Emilia, Nur F.; Nurlaili, Efi; Rovik, Anwar; Ansori, Arif NM.; Parikesit, Arli A.; Chatterjee, Shrabonti; Mahata, Joydeep; Firdous, Athika; Sahadewa, Sukma; Khairullah, Aswin R.; Adnyana, I MDM.; Rebezov, Maksim; Abdurasulov, Abdugani; Durry, Fara D.; Rollando, Rollando
Narra X Vol. 4 No. 1 (2026): April 2026 (In Press)
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narrax.v4i1.263

Abstract

Rabies remains a neglected zoonotic disease with disproportionately high incidence and mortality across African regions, highlighting the need for improved and population-tailored preventive strategies. The aim of this study was to design and evaluate a multi-epitope rabies vaccine candidate targeting the rabies virus glycoprotein using a reverse vaccinology and immunoinformatics approach, with consideration of African human leukocyte antigen (HLA) allele diversity. A total of eleven cytotoxic T-lymphocyte (CTL), nine helper T-lymphocyte (HTL), and nine B-cell linear epitopes were predicted and subsequently filtered based on immunogenicity, interferon-gamma (IFN-γ) induction potential, antigenicity, allergenicity, and toxicity. The selected epitopes were assembled into a vaccine construct using appropriate adjuvants and immunostimulatory linkers. Population coverage analysis demonstrated a high theoretical coverage of 99.95% across five African subregions, underscoring the advantage of region-specific vaccine design. The final construct exhibited favorable physicochemical properties, including an instability index of 29.00 and a Grand Average of Hydropathy (GRAVY) score of -0.304, indicating stability and hydrophilicity. Structural validation showed 95.6% residues in favored regions of the Ramachandran plot, with an ERRAT score of 98.86 and a ProSA Z-score of -3.26. Molecular docking with toll-like receptor 4 (TLR4) revealed strong binding interactions, including 35 hydrogen bonds and ten salt bridges. Immune simulation predicted robust humoral and cellular responses with memory cell formation, while normal mode analysis supported structural stability and flexibility. Furthermore, the construct was successfully codon-optimized (codon adaptation index: 0.97; GC content: 51%) and in silico cloned into the pET-28a(+) vector, indicating potential for expression in Escherichia coli. These findings support the theoretical feasibility of a population-specific rabies vaccine candidate and warrant further experimental validation.
Co-Authors Abdurasulov, Abdugani Ade Irene Beactris Saudale Adi Hermansyah, Adi Adi Sofyan Ansori, Muhammad Adnyana, I MDM. Afnani, Moh R. Aini, Nur Sofiatul Alfanaar, Rokiy Anastasia Risvina Easter Ajie Pramesti Ansori, Arif NM. Arum Ardanareswari Atarodang Beatrico Lyo Ayu Merli Wahyuni Aziz, Nur Bella Vania Sianto Benedictus Karel Bezhinar, Tatyana Burkov, Pavel Chandra, Melisa Dwi Charina Halim Sugiono Chatterjee, Shrabonti Chresiani Destianita Yoedistira Chresiani Destianita Yoedistira Chresiani Destianita Yoedistira Christopher Daniel Kurniawan Collins, Ellen Derkho, Marina Dhanang Prawira Nugraha Dhita Rizki Amalia Dion Notario Dion Notario Dodi Iskandar Dodi Iskandar, Dodi Durry, Fara D. E. Monica Eka Anggie Amalia Eka Anggie Amalia Emilia, Nur F. Erizcha Debora Embang Erlinawati Santoso Erlinawati Santoso Eva Monica Eva Monica Eva Monica Eva Monica, Eva Fauziya Radani Fibe Yulinda Cesa Firdous, Athika FX Haryanto Susanto Godeliva Adriani Hendra Gudz, Petr Gytha Novella Ongkowijoyo Herdiansyah, Mochammad Aqilah Hery Purnobasuki Ichsan Ichsan Indriani Nuraini Widya Ismaurasi, Marcelina Fransisca Alecia Kestrilia Rega Prilianti Khairullah, Aswin R. Khairullah, Aswin Rafif Kharisma, Viol Dhea Kotimah, Chusnul Lealita Leny Yuliati Mahata, Joydeep Maksimiuk, Nikolai Maria Sindy Marsha Anggita Amelia Martanty Aditya, Martanty Masruri Masruri Masruri Masruri Maywan Hariono Mifta Devin Suwandi Monica, Eva Muhammad Hilmi Afthoni Muhammad Setiyawan Munawir Sazali Murtadlo, Ahmad Affan Ali Nashi Widodo Nashi Widodo Natanael Anugerah Tuuk Natan Nugraha, Dhanang Prawira Nurlaili, Efi Nurmiati Nurul Azmi Wibawanty P. N. Alfiyandri Parikesit, Arli A. Paulina Genoveva Moza Pramesti, Agatha Tri Endha Rahadi, Theresa Dhea Lonika Raharja, Albert Rebezov, Maksim Rehmadanta Sitepu Rehmadanta Sitepu Rehmadanta Sitepu Rehmadanta Sitepu Rehmadenta Sitepu Renata Hadi Resha Ramadhania Rino Tam Cahyadi, Rino Tam Ririn Nurdiani Ririn Nurdiani Rovik, Anwar Ruth Febriana Kesuma Sabrina Handayani Tambun Sandra Dewi Tansil Setiawan, Hendry Siswadi Siswadi Sitepu, Rehmadanta Sitepu, Rehmadanta Sophia Yusnita Wahyu Timur Sophia Yusnita Wahyu Timur Sri Hardyastutik Sugiono, Charina Halim Suharyani Amperawati Sukma Sahadewa, Sukma Susana Susana Susanto, FX. Haryanto Teguh Hari Sucipto, Teguh Hari Trianom Suryandharu W. Swastika Wahyu Timur, Sophia Yusnita Warsito Warsito Warsito Warsito Widyananda, Muhammad Hermawan Windra Swastika Windra Swastika Y. Erning Indrastuti Yandriyani, Devilke Yanuar, Michael Resta Surya Yuni Purwaningdiah Yurida Ekawati Yurida Ekawati Yuyun Yuniati